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Innovation in Basic Science: Stem Cells and their role in the treatment of Paediatric Cardiac Failure – Opportunities and Challenges

Published online by Cambridge University Press:  01 November 2009

Sunjay Kaushal ,
Jeffrey Phillip Jacobs ,
Jeffrey G. Gossett ,
Ann Steele ,
Peter Steele ,
Craig R. Davis ,
Elfriede Pahl ,
Kalpana Vijayan ,
Alfred Asante-Korang  and
Robert J. Boucek
...Show all authors
Sunjay Kaushal*
Affiliation:
Divisions of Cardiovascular-Thoracic Surgery, Children’s Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
Jeffrey Phillip Jacobs
Affiliation:
The Congenital Heart Institute of Florida (CHIF), Division of Thoracic and Cardiovascular Surgery, All Children’s Hospital and Children’s Hospital of Tampa, University of South Florida College of Medicine, Cardiac Surgical Associates of Florida (CSAoF), Saint Petersburg and Tampa, Florida, United States of America
Jeffrey G. Gossett
Affiliation:
Division of Cardiology, Children’s Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
Ann Steele
Affiliation:
The Congenital Heart Institute of Florida (CHIF), All Children’s Hospital, Saint Petersburg, Florida, United States of America
Peter Steele
Affiliation:
The Congenital Heart Institute of Florida (CHIF), All Children’s Hospital, Saint Petersburg, Florida, United States of America
Craig R. Davis
Affiliation:
Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Children’s Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio, United States of America
Elfriede Pahl
Affiliation:
Division of Cardiology, Children’s Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
Kalpana Vijayan
Affiliation:
Divisions of Cardiovascular-Thoracic Surgery, Children’s Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
Alfred Asante-Korang
Affiliation:
The Congenital Heart Institute of Florida (CHIF), Division of Pediatric Cardiology, All Children’s Hospital and Children’s Hospital of Tampa, Saint Petersburg and Tampa, Florida, United States of America
Robert J. Boucek
Affiliation:
Seattle Children’s Hospital and the University of Washington, Seattle, Washington, United States of America
Carl L. Backer
Affiliation:
Divisions of Cardiovascular-Thoracic Surgery, Children’s Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
Loren E. Wold
Affiliation:
Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Children’s Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio, United States of America
*
Correspondence to: Dr Kaushal, PhD, MD, Division of Cardiovascular-Thoracic Surgery, Children’s Memorial Hospital, 2300 Children’s Plaza, mc 22, Chicago, Illinois, United States of America. Tel: 773-880-4378; Fax: 773-880-3054; E-mail: skaushal@childrensmemorial.org
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Abstract

Heart failure is a leading cause of death worldwide. Current therapies only delay progression of the cardiac disease or replace the diseased heart with cardiac transplantation. Stem cells represent a recently discovered novel approach to the treatment of cardiac failure that may facilitate the replacement of diseased cardiac tissue and subsequently lead to improved cardiac function and cardiac regeneration.

A stem cell is defined as a cell with the properties of being clonogenic, self-renewing, and multipotent. In response to intercellular signalling or environmental stimuli, stem cells differentiate into cells derived from any of the three primary germ layers: ectoderm, endoderm, and mesoderm, a powerful advantage for regenerative therapies. Meanwhile, a cardiac progenitor cell is a multipotent cell that can differentiate into cells of any of the cardiac lineages, including endothelial cells and cardiomyocytes.

Stem cells can be classified into three categories: (1) adult stem cells, (2) embryonic stem cells, and (3) induced pluripotential cells. Adult stem cells have been identified in numerous organs and tissues in adults, including bone-marrow, skeletal muscle, adipose tissue, and, as was recently discovered, the heart. Embryonic stem cells are derived from the inner cell mass of the blastocyst stage of the developing embryo. Finally through transcriptional reprogramming, somatic cells, such as fibroblasts, can be converted into induced pluripotential cells that resemble embryonic stem cells.

Four classes of stem cells that may lead to cardiac regeneration are: (1) Embryonic stem cells, (2) Bone Marrow derived stem cells, (3) Skeletal myoblasts, and (4) Cardiac stem cells and cardiac progenitor cells. Embryonic stem cells are problematic because of several reasons: (1) the formation of teratomas, (2) potential immunologic cellular rejection, (3) low efficiency of their differentiation into cardiomyocytes, typically 1% in culture, and (4) ethical and political issues. As of now, bone marrow derived stem cells have not been proven to differentiate reproducibly and reliably into cardiomyocytes. Skeletal myoblasts have created in vivo myotubes but have not electrically integrated with the myocardium. Cardiac stem cells and cardiac progenitor cells represent one of the most promising types of cellular therapy for children with cardiac failure.

Keywords

Stem cellpaediatricsheart failureembryonic stem cellbone marrow
Type
Original Article
Information
Cardiology in the Young , Volume 19 , Issue S2: Innovation associated with the treatment of patients with congenital and pediatric cardiac disease , November 2009 , pp. 74 - 84
Copyright
Copyright © Cambridge University Press 2009

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